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2054363 
Journal Article 
Bioavailability of the oral selective phosphodiesterase 4 inhibitor cilomilast 
Zussman, BD; Davie, CC; Kelly, J; Murdoch, RD; Clark, DJ; Schofield, JP; Walls, C; Birrell, C; Webber, D; Quinlan, J; Ritchie, SY; Carr, A 
2001 
1 
Pharmacotherapy
ISSN: 0277-0008
EISSN: 1875-9114 
21 
6 
653-660 
English 
11401178 
WOS:000170849200001 
STUDY OBJECTIVE: To determine the absolute bioavailability of cilomilast, and assess the effects of food, dosing time, and coadministration of antacid agents on its bioavailability and pharmacokinetics in healthy volunteers.

SETTING: Clinical pharmacology unit.

DESIGN: Five prospective pharmacokinetic studies: one single-blind, dose-escalating, placebo-controlled trial; four open-label, randomized studies.

SUBJECTS: Ninety-six healthy adult volunteers who were nonsmokers.

INTERVENTION: In the first study, four subjects received intravenous cilomilast 1, 2, and 4 mg. In the second study, 16 subjects received oral cilomilast 15 mg or intravenous cilomilast 4 mg. In the other three studies, a total of 76 subjects were given single oral 15-mg doses; one study compared its effects in fed versus fasted subjects, one looked for differences of morning versus evening dosing, and one examined coadministration with aluminum hydroxide-magnesium hydroxide.

MEASUREMENTS AND MAIN RESULTS: After intravenous administration of cilomilast, plasma concentrations increased in an approximately dose-proportional manner; the half-life, approximately 6.5 hours, was dose independent. Cilomilast clearance and volume of distribution were small. After oral dosing, the absolute bioavailability was consistently close to 100%. Absorption was slower in fed subjects than in fasted (median 2-hr delay in time to reach maximum plasma concentration, average 39% reduction in maximum plasma concentration), but the area under the concentration-time curve from time zero to infinity (systemic availability) was unaffected. Pharmacokinetic parameters were not influenced by time of dosing or coadministration of antacid.

CONCLUSION: The absolute bioavailability of oral cilomilast was 100%; it was not adversely affected by time of dosing or coadministration with food or antacid.